Cell Reports Medicine (Sep 2020)
Robust T Cell Response Toward Spike, Membrane, and Nucleocapsid SARS-CoV-2 Proteins Is Not Associated with Recovery in Critical COVID-19 Patients
- Constantin J. Thieme,
- Moritz Anft,
- Krystallenia Paniskaki,
- Arturo Blazquez-Navarro,
- Adrian Doevelaar,
- Felix S. Seibert,
- Bodo Hoelzer,
- Margarethe Justine Konik,
- Marc Moritz Berger,
- Thorsten Brenner,
- Clemens Tempfer,
- Carsten Watzl,
- Toni L. Meister,
- Stephanie Pfaender,
- Eike Steinmann,
- Sebastian Dolff,
- Ulf Dittmer,
- Timm H. Westhoff,
- Oliver Witzke,
- Ulrik Stervbo,
- Toralf Roch,
- Nina Babel
Affiliations
- Constantin J. Thieme
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, BIH Center for Regenerative Therapies, Berlin, Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Medical Immunology, Berlin, Berlin, Germany
- Moritz Anft
- Ruhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, Germany
- Krystallenia Paniskaki
- Ruhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, Germany
- Arturo Blazquez-Navarro
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, BIH Center for Regenerative Therapies, Berlin, Berlin, Germany; Ruhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, Germany
- Adrian Doevelaar
- Ruhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, Germany
- Felix S. Seibert
- Ruhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, Germany
- Bodo Hoelzer
- Ruhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, Germany
- Margarethe Justine Konik
- University Duisburg-Essen, University Hospital Essen, Department of Infectious Diseases, West-German Centre for Infectious Diseases, Essen, North Rhine-Westphalia, Germany
- Marc Moritz Berger
- University Duisburg-Essen, University Hospital Essen, Department of Anesthesiology and Intensive Care Medicine, Essen, North Rhine-Westphalia, Germany
- Thorsten Brenner
- University Duisburg-Essen, University Hospital Essen, Department of Anesthesiology and Intensive Care Medicine, Essen, North Rhine-Westphalia, Germany
- Clemens Tempfer
- Ruhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Department of Gynecology and Obstetrics, Herne, North Rhine-Westphalia, Germany
- Carsten Watzl
- Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund (IfADo), Department of Immunology Dortmund, North Rhine-Westphalia, Germany
- Toni L. Meister
- Ruhr-University Bochum, Department of Molecular and Medical Virology, Bochum, North Rhine-Westphalia, Germany
- Stephanie Pfaender
- Ruhr-University Bochum, Department of Molecular and Medical Virology, Bochum, North Rhine-Westphalia, Germany
- Eike Steinmann
- Ruhr-University Bochum, Department of Molecular and Medical Virology, Bochum, North Rhine-Westphalia, Germany
- Sebastian Dolff
- University Duisburg-Essen, University Hospital Essen, Department of Infectious Diseases, West-German Centre for Infectious Diseases, Essen, North Rhine-Westphalia, Germany
- Ulf Dittmer
- University Duisburg-Essen, University Hospital Essen, Institute for Virology, Essen, North Rhine-Westphalia, Germany
- Timm H. Westhoff
- Ruhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, Germany
- Oliver Witzke
- University Duisburg-Essen, University Hospital Essen, Department of Infectious Diseases, West-German Centre for Infectious Diseases, Essen, North Rhine-Westphalia, Germany
- Ulrik Stervbo
- Ruhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, Germany
- Toralf Roch
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, BIH Center for Regenerative Therapies, Berlin, Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Medical Immunology, Berlin, Berlin, Germany; Ruhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, Germany
- Nina Babel
- Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, BIH Center for Regenerative Therapies, Berlin, Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Medical Immunology, Berlin, Berlin, Germany; Ruhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, Germany; Corresponding author
- Journal volume & issue
-
Vol. 1,
no. 6
p. 100092
Abstract
Summary: T cell immunity toward SARS-CoV-2 spike (S-), membrane (M-), and nucleocapsid (N-) proteins may define COVID-19 severity. Therefore, we compare the SARS-CoV-2-reactive T cell responses in moderate, severe, and critical COVID-19 patients and unexposed donors. Overlapping peptide pools of all three proteins induce SARS-CoV-2-reactive T cell response with dominance of CD4+ over CD8+ T cells and demonstrate interindividual immunity against the three proteins. M-protein induces the highest frequencies of CD4+ T cells, suggesting its relevance for diagnosis and vaccination. The T cell response of critical COVID-19 patients is robust and comparable or even superior to non-critical patients. Virus clearance and COVID-19 survival are not associated with either SARS-CoV-2 T cell kinetics or magnitude of T cell responses, respectively. Thus, our data do not support the hypothesis of insufficient SARS-CoV-2-reactive immunity in critical COVID-19. Conversely, it indicates that activation of differentiated memory effector T cells could cause hyperreactivity and immunopathogenesis in critical patients.
